This was considered important knowing the homing characteristics of pDC to the T-cell area in the activated lymph nodes. Interestingly, both IFN-c the major Th1 and IL-4 the major Th2 cytokine promoted pDC activation and survival. This indicates that the Th1/Th2 system does not imprint a particular bias on pDC but rather AbMole Seratrodast supports their function during a T-cell response. Nevertheless, it should be noted that porcine IL4 has been reported to functionally differ from human and mouse IL-4 at least with respect to its ability to promote B-cell activation and this author has questioned the role of IL-4 in the porcine Th1Th2 paradigm. Furthermore, IL-4 has been difficult to detect, both at the protein and mRNA level, in vitro and in vivo. It is possible that in particular breeds of pigs IL-13 could have a more prominent role for porcine Th2 responses. On the other hand, both IL-4 and IL-13 are able to induce the generation of monocytes-derived DC in the pig and to prevent apoptosis of endothelial cells. Independent of this issue requiring further clarification, pDC are more likely to promote Th1 responses through secretion of type I IFNs, IL-12 and TNF-a. We and others have also found this profile of cytokines for porcine pDC. As expected from studies with other species, the antiinflammatory cytokine IL-10 represents a main negative regulator of porcine pDC. This cytokine is produced by regulatory T cells, and many other cells such as monocytes/macrophages, B cells and DC during the terminal phase of an immune response, where it has important anti-inflammatory functions to prevent unnecessary tissue damage caused by the immune system. Interestingly, pDC have been reported to control B-cell-derived IL-10 production, which together with the strong effects of IL-10 on pDC activation would fit into the concept of a vicious circle of chronic pDC activation such as described during systemic lupus erythemathosus. Considering the necessity to regulate innate immune responses to avoid damaging effects of IFN-a during infections, it is not surprising that other cytokines such as include prostaglandin E2 and transforming growth factor-b which counter-regulate pDC responses have been described. Their effect on porcine pDC was not addressed in the present study, but we expect a suppression of IFN-a responses as in other species. Taken together, the knowledge on how cytokines regulate pDC responses can be employed to modulate the immune response towards a wanted direction. Considering the importance of type-I IFN as endogenous immunological adjuvant, cytokines could for instance be used to enhance pDC-derived type-I IFN during vaccination. Another area would be to employ such knowledge for immunotherapies of cancer, chronic virus infections and autoimmune diseases where pDC responses can be beneficial or unwanted.Peroxisome proliferator activated receptor-d, a member of the ligand-activated PPAR nuclear receptor family.